This proposal aims to study the regulation of biosynthesis of human placental lactogen (hPL), its processing and secretion in placentas from gestational diabetics as compared with normals. It has been shown that high levels of serum hPL in third trimester of pregnancy are closely related to diabetes. The experimental approach is to study hPL biosynthesis, processing and secretion in explants from placentas of gestationally diabetic women with special emphasis on the regulation of mRNA translation as measured by half translation time. For this we plan to employ specific antibody affinity chromatography. In addition the hPL mRNA will be translated in rabbit reticulocyte cell-free system in order to quantitate the translatable hPL mRNA and to analyze the regulation of the processing of the prehormone. Quantitation of hPL mRNA in gestation diabetes will also be accomplished using hybridization to hPL cDNA. It is well established that women suffering from gestational diabetes are most likely to develop diabetes mellitus later in life. Therefore, a better understanding of the mechanism responsible for gestational diabetes may bring about a better management of this disease. This, in turn, may help to prevent the development of diabetes mellitus in these women.